Basis of Gene Therapy

By present time safety problems of gene therapy are widely discussed among scientists of all world. In this review results of clinical researches are summarized; explanations concerning side effects of vectors integration are given; factors that can cause genotoxicity are discussed. Approaches which can save or increase clinical efficacy of gene therapy with use as targets hematopoietic stem cells, thus significantly reduced risk of leukemia development and other side effects related to vectors including in genome, are presented

Influence of an Ante- and Intranatal Factors on Cord Blood Cell Composition of Fullterm Newborns

The hypoxia is the powerful stressful factor, and, presumably, should result not only in rising of erythrocytes counts for the compensatory purpose, but also in rising of other blood cells number, as consequence of mobilization in the answer stress. In article the influence assessment of pregnancy and delivery features, acute and chronic fetal hypoxia on cord blood cell composition of the full-term newborns is shown. Increase of leucocytes count at elongation of the second period of delivery, presence of chronic prenatal hypoxia or acute hypoxia in delivery is revealed. Differences of cord blood cell composition depending on newborn gender and body weight which consist in higher leucocytes count (all subpopulations including hematopoietic stem cells) at boys and at higher body weight are shown. Differences according to gender and to body weight are independent from each other. It is shown, that boys worse adapt for delivery that is expressed in higher concentration of mobilization cytokines and higher leucocytes and hemopoietic progenitors count in cord blood. It is shown, that mobilization cytokine concentration (IL-8, G-CSF, MMP-9) in cord blood of full-term newborns statistically significantly above, than in peripheral blood of healthy donors. Thus IL-8, G-CSF, MMP-9 concentration higher at boys in comparison with girls; at normal delivery in comparison with delivery by planned cesarean sections and at acute fetal hypoxia

Cell Composition of Cord Blood and G-Scf-Mobilized Blood Transplantational Material

Cord blood cell composition is a short-lasting delivery stress consequence and is similar on adult G-CSF-mobilized peripheral blood. G-SCF realizes biological effect by number of secondary messengers, many of which are also natural effectors of stress. In this research comparative characteristics of cell composition, including lymphocytes subpopulations, CD34+ and CD133+ cells, hematopoietic progenitor cells colony-forming activity and mobilizing cytokines concentration (IL-8, MMP-2, MMP-9), between term newborns cord blood and G-SCF-mobilized peripheral blood is shown. Mobilized cytokines concentration ratio in combination with CD34+ cells count in cord blood and mobilized peripheral blood suggests that delivery stress possibly is not single cause of cord blood features

Performance and scalability of the back-end sub-system in the ATLAS DAQ/EF prototype

The DAQ group of the future ATLAS experiment has developed a prototype system based on the trigger/DAQ architecture described in the ATLAS Technical Proposal to support studies of the full system functionality, architecture as well as available hardware and software technologies. One sub-system of this prototype is the back- end which encompasses the software needed to configure, control and monitor the DAQ, but excludes the processing and transportation of physics data. The back-end consists of a number of components including run control, configuration databases and message reporting system. The software has been developed using standard, external software technologies such as OO databases and CORBA. It has been ported to several C++ compilers and operating systems including Solaris, Linux, WNT and LynxOS. This paper gives an overview of the back-end software, its performance, scalability and current status. (17 refs)

Pathway Instability Is an Effective New Mutation-Based Type of Cancer Biomarkers

DNA mutations play a crucial role in cancer development and progression. Mutation profiles vary dramatically in different cancer types and between individual tumors. Mutations of several individual genes are known as reliable cancer biomarkers, although the number of such genes is tiny and does not enable differential diagnostics for most of the cancers. We report here a technique enabling dramatically increased efficiency of cancer biomarkers development using DNA mutations data. It includes a quantitative metric termed Pathway instability (PI) based on mutations enrichment of intracellular molecular pathways. This method was tested on 5,956 tumor mutation profiles of 15 cancer types from The Cancer Genome Atlas (TCGA) project. Totally, we screened 2,316,670 mutations in 19,872 genes and 1,748 molecular pathways. Our results demonstrated considerable advantage of pathway-based mutation biomarkers over individual gene mutation profiles, as reflected by more than two orders of magnitude greater numbers by high-quality [ROC area-under-curve (AUC)>0.75] biomarkers. For example, the number of such high-quality mutational biomarkers distinguishing between different cancer types was only six for the individual gene mutations, and already 660 for the pathway-based biomarkers. These results evidence that PI value can be used as a new generation of complex cancer biomarkers significantly outperforming the existing gene mutation biomarkers

Acute Progression of BCR-FGFR1 Induced Murine B-Lympho/Myeloproliferative Disorder Suggests Involvement of Lineages at the Pro-B Cell Stage

Constitutive activation of FGFR1, through rearrangement with various dimerization domains, leads to atypical myeloproliferative disorders where, although T cell lymphoma are common, the BCR-FGFR1 chimeric kinase results in CML-like leukemia. As with the human disease, mouse bone marrow transduction/transplantation with BCR-FGFR1 leads to CML-like myeloproliferation as well as B-cell leukemia/lymphoma. The murine disease described in this report is virtually identical to the human disease in that both showed bi-lineage involvement of myeloid and B-cells, splenomegaly, leukocytosis and bone marrow hypercellularity. A CD19+ IgM− CD43+ immunophenotype was seen both in primary tumors and two cell lines derived from these tumors. In all primary tumors, subpopulations of these CD19+ IgM− CD43+ were also either B220+ or B220−, suggesting a block in differentiation at the pro-B cell stage. The B220− phenotype was retained in one of the cell lines while the other was B220+. When the two cell lines were transplanted into syngeneic mice, all animals developed the same B-lymphoblastic leukemia within 2-weeks. Thus, the murine model described here closely mimics the human disease with bilineage myeloid and B-cell leukemia/lymphoma which provides a representative model to investigate therapeutic intervention and a better understanding of the etiology of the disease

Программный комплекс для исследования удаленных междуфазных замыканий на линиях 6–10 (35) кВ с односторонним питанием

The paper considers methodology for creation of software complex while using Fortran software modules and DELPHI object programming system. Software complex is designed for investigation of line operational modes of 6–10 (35) kW with supply on one side and remote inter-phase short circuits. Рассматривается методика создания программного комплекса с использованием фортрановских программных модулей и системы объектного программирования DELРНI. Программный комплекс предназначен для исследования режимов работы линий 6–10 (35) кВ с односторонним питанием при удаленных междуфазных замыканиях

О выборе характеристик срабатывания токовых защит линий в распределительных сетях с односторонним питанием

A brief analysis of operational characteristics of current protection with various current-time curves of distributive network lines with unsoldering is given in the paper. The paper considers possible measures directed on better technical modernization and expansion in the field of application of multi-stage microprocessor current protection in distributive networks with one-side power supply.Выполнен краткий анализ характеристик срабатывания токовых защит с различными времятоковыми характеристиками линий распределительной сети с отпайками. Рассмотрены возможные мероприятия по повышению технического совершенства и расширению области использования многоступенчатых микропроцессорных токовых защит в распределительных сетях с односторонним питанием

Novel robust biomarkers for human bladder cancer based on activation of intracellular signaling pathways

Sherpa Romeo blue journal. Open access article. Creative Commons Attribution 3.0 License (CC BY 3.0) applies.We recently proposed a new bioinformatic algorithm called OncoFinder for quantifying the activation of intracellular signaling pathways. It was proved advantageous for minimizing errors of high-throughput gene expression analyses and showed strong potential for identifying new biomarkers. Here, for the first time, we applied OncoFinder for normal and cancerous tissues of the human bladder to identify biomarkers of bladder cancer. Using Illumina HT12v4 microarrays, we profiled gene expression in 17 cancer and seven non-cancerous bladder tissue samples. These experiments were done in two independent laboratories located in Russia and Canada. We calculated pathway activation strength values for the investigated transcriptomes and identified signaling pathways that were regulated differently in bladder cancer (BC) tissues compared with normal controls. We found, for both experimental datasets, 44 signaling pathways that serve as excellent new biomarkers of BC, supported by high area under the curve (AUC) values. We conclude that the OncoFinder approach is highly efficient in finding new biomarkers for cancer. These markers are mathematical functions involving multiple gene products, which distinguishes them from “traditional” expression biomarkers that only assess concentrations of single genes.Ye

ПОВЫШЕНИЕ ТЕХНИЧЕСКОГО СОВЕРШЕНСТВА ТОКОВЫХ И ТОКОВЫХ НАПРАВЛЕННЫХ ЗАЩИТ РАСПРЕДЕЛИТЕЛЬНЫХ СЕТЕЙ

The paper considers principles of execution and methods for investigation of adaptive micro-processor protection of distributive systems with one- and two-side supply. Adaptive current protection  for the systems with one-side supply controls a moment  of non-symmetric  damage  initiation and automatically operate current of measuring elements. Systems with two-side supply presuppose combined usage of methods for determination of damage places and conventional method for execution of protection.Рассматриваются принципы выполнения и методы исследования адаптивных микропроцессорных защит распределительных сетей с одно- и двусторонним питанием. Адаптивная токовая защита для сетей с односторонним питанием контролирует момент  наступления  несимметричного повреждения и автоматически ток срабатывания измерительных органов. В сетях с двусторонним питанием предлагается комбинированное использование методов определения мест повреждений и традиционных методов выполнения защиты